P1489: MANAGEMENT OF SICKLE CELL DISEASE WITH HYDROXYUREA: A SYSTEMATIC REVIEW FROM LOW- AND MIDDLE-INCOME COUNTRIES
Authors: V. Paintsil, K. Marfo, F. Adisa, S. Khan, L. M. Tshilolo
Journal: HemaSphere (2022)

Background: Clinical trials conducted in Africa have demonstrated the safe and effective use of hydroxyurea (HU) for sickle cell disease (SCD) children in low-resource settings. Despite WHO listing of HU as essential medicine, it’s clinical use is limited in LMICs with high disease burden. Aims: We aim to assess the available literature on the clinical efficacy, safety and real-word effectiveness with HU therapy in LMICs. Here we present the preliminary observation from the clinical studies. Methods: This systematic literature review was performed using Embase, PubMed, OVID and Web of Science, in English between January 2000–2022. Clinical and real-world studies assessing therapy with HU in patients with SCD were considered. Results: Of 3709 studies identified in the search, 124 unique studies with 20 clinical trials were included (Figure). There is a dearth of studies from Asian countries, and majority of the included studies are from sub-Saharan Africa (SSA) and Latin America. In these regions the initial dose of HU ranged from 10–25 mg/kg/day and the most common initial dose was 15–20 mg/kg/day. The maximum tolerated dose (MTD) of HU studied was 25–35 mg/kg/day; however, few studies on stroke prevention used MTD of 40 mg/kg/day. As anticipated, significant increases in haemoglobin (Hb), foetal haemoglobin (HbF) and mean corpuscular volume levels were reported both with fixed (20 mg/kg/day) as well as escalated dose (≤35 mg/kg/day) across various subgroups. Treatment with HU at doses 15–30 mg/kg/day was shown to reduce the need for transfusions, and few studies reported that no transfusions were required during the treatment period. HU treatment initiation also reported reduction in vaso-occlusive crisis (VOC)–related pain episodes; treatment for only 6 months across fixed doses of 15–20 mg/kg/day has resulted in significant reduction in VOC-related pain. HU therapy reduced abnormally high transcranial Doppler velocities, was associated with a significantly lower risk of conversion to abnormal time-averaged maximum mean velocities and prevented the risk of primary stroke in SCD patients. The use of low-dose HU therapy (10 mg/kg/day) for children with SCD was also beneficial in primary stroke prevention. The HU dose of 30–40 mg/kg/day in children for a period of 3.5–9.3 years was effective in preventing secondary stroke with no risk of toxicity. Treatment with HU for a year with fixed dose of 20 mg/kg/day was associated with lower stroke recurrence rates if started within 2 months of initial stroke. Significant reduction in malaria events and related hospitalisations were associated with HU. Treatment for 2 years at a dose of 20 mg/kg/day in young infants (median age 15 months) was also reported to be well tolerated and effective in improving Hb and HbF levels and delaying functional asplenia. Clinical safety of HU is long well-established, and no new safety signals were reported. The myelosuppression observed with HU treatment was mostly transient in nature but required regular monitoring which can be challenging in LMICs. Image:Summary/Conclusion: Our preliminary findings showed that in patients with SCD from LMICs especially SSA and Latin American regions, HU was well tolerated and effective in improving haematological outcomes, lowering VOC and malaria events, and reducing primary/recurrent stroke risks. HU treatment was also effective and safe in young infants (≥ 9 months of age). Treatment initiation with HU reduced the need for transfusions, which can be beneficial for SCD management in these resource-limited countries.